Influenza, an illness caused by respiratory infection with influenza viruses, often occurs in winter. It is known to have very high infectivity and to affect all age groups, particularly elderly people (Treanor J, 2004, N Engl J Med. 350(3):218-20). Influenza viruses are enveloped RNA (ribonucleic acid) viruses belonging to the family Orthomyxoviridae and have a genome composed of eight negative-sense, single-stranded RNA (ribonucleic acid) segments. These influenza viruses are classified into types A, B and C. Influenza A viruses are further divided into subtypes based on their major surface proteins hemagglutinin (HA) and neuraminidase (NA). Up to date, 16 HAs and 9 NAs have been identified (Cheung T K and Poon L L 2007, Ann N Y Acad Sci. 1102:1-25). Influenza viruses can affect birds, pigs and humans depending on their types and have a genome composed of RNA segments, and for this reason, their genes can continuously mutate and recombine, resulting in new genetic variations (Treanor J, 2004. N Engl J Med. 350(3):218-20). Due to this continuous mutation, it is difficult to obtain permanent immunity against influenza viruses, and thus a preventive method that is currently thought to be most effective is a method of administering a vaccine against a particular type of influenza viruses expected to be prevalent each year to develop immunity against the influenza virus each year.
Vaccines against influenza viruses are generally produced using eggs, but this production method is a time-consuming and inefficient method. Accordingly, this method has a problem in that it is difficult to produce sufficient amounts of vaccines each year within a limited time frame. In an attempt to solve this problem, studies on methods of producing vaccines by cell culture have been actively conducted by several pharmaceutical companies (GSK, Baxter, etc.). In addition, if pandemic influenza virus infection occurs, it is very difficult to develop a vaccine against the infection within a short time. Also, antiviral drugs are not completely reliable due to a problem associated with the emergence of drug-resistant mutant viruses.
To overcome this problem, antibodies against influenza viruses have recently been actively developed (Throsby et al, 2008, PloS One 3 (e3942); Sui et al., 2009, Nature structural & molecular biology. 16 (265-273); Simmons et al, 2007, PloS Medicine 4 (e178); Wrammert et al., 2011, J Exp Med. 208 (181-193); Corti et al., 2011, Science 333 (850-856)).
Blood products from recovered patients have been used to treat patients infected with various viruses, as well as to treat pandemic flu infections. For example, when patients infected with Spanish influenza virus had symptoms of pneumonia, blood products collected from patients who recovered from infection with the influenza virus are used to treat the influenza virus (Luke et al., 2006. Annals of internal medicine. 145:599). As such, hyperimmune globulin (IgIv) is purified from human plasma and used to treat patients infected with various viruses, but the product obtained as described above may not be safe from potential infectious agents in blood and is inefficient for mass production.
Human B cells are used for the screening of specific human monoclonal antibodies. However, immortalization of human B cells by Epstein-Barr virus (EBV) is less efficient and time-consuming. To overcome this shortcoming, new techniques have been developed and used. One of these techniques is the use of an RT-PCR method to obtain genetic information for an antibody directly from B cells. For example, there is a method comprising staining B cells that express an antibody to a specific antigen, isolating the B cells using a FACS sorter, obtaining genetic information for the antibody from the single B cells by an RT-PCR method, inserting the genetic information into an expression vector, and transfecting the expression vector into animal cells to produce a large amount of the antibody. To perform this production method in an easier and more rapid manner, the following technique can be used. The new technique “immunospot array assay on a chip” (ISAAC) enables an antibody gene to be obtained by screening single B cells, which secrete a specific monoclonal antibody, within several weeks (Jin et al., 2009 Nat Med. 15, 1088-1092). The antibody thus obtained is a natural human antibody which can be more effective in terms of immunogenic issues.